Infiltrating T lymphocytes and programmed cell death protein-1/programmed death-ligand 1 expression in endometriosis-associated ovarian cancer

Fertil Steril. 2022 Jan;117(1):160-168. doi: 10.1016/j.fertnstert.2021.08.032. Epub 2021 Oct 14.

Abstract

Objective: To characterize T lymphocyte infiltration and programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression in early-stage endometriosis-associated ovarian cancer (EAOC), ovarian endometriosis (OE), atypical endometriosis (AE), and deep endometriosis (DE).

Design: Case-control, retrospective study.

Setting: Research University Hospital.

Patient(s): A total of 362 patients with a histologic diagnosis of EAOC, OE, AE, or DE were identified between 2000 and 2019 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Gemelli Molise SpA tissue data banks. A 1:1 propensity score-matched method yielded matched pairs of 55 subjects with EAOC, 55 patients with OE, 12 patients with AE, and 42 patients with DE, resulting in no differences in family history of cancer, parity, and use of oral contraceptives.

Intervention(s): Immunohistochemistry assays using the following primary antibodies: CD3+; CD4+; CD8+; PD-1; and PD-L1.

Main outcome measure(s): To characterize T lymphocyte infiltration and PD-1/PD-L1 expression in 4 different endometriosis-related diseases.

Result(s): Endometriosis-associated ovarian cancer cases displayed significantly higher levels of PD-1/PD-L1 expression compared with all other endometriosis-related diseases (vs. OE vs. AE vs. DE). Moreover, a significantly lower count of infiltrating T lymphocytes was observed in EAOC cases compared with OE ones. Finally, one-third of OE cases showed a cancer-like PD-1/PD-L1 expression profile.

Conclusion(s): Endometriosis-associated ovarian cancer is characterized by higher levels of PD-1/PD-L1 expression compared with benign endometriosis-related diseases. This profile was found in one-third of clinically benign cases, suggesting that it develops early in the carcinogenesis process.

Keywords: Endometriosis; PD-1; PD-L1; endometriosis-associated ovarian cancer; infiltrating lymphocytes.

MeSH terms

  • Adult
  • B7-H1 Antigen / metabolism
  • Carcinoma, Ovarian Epithelial / etiology
  • Carcinoma, Ovarian Epithelial / immunology
  • Carcinoma, Ovarian Epithelial / metabolism
  • Case-Control Studies
  • Cell Movement / immunology
  • Chemotaxis, Leukocyte / physiology
  • Endometriosis / complications*
  • Endometriosis / immunology
  • Endometriosis / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Italy
  • Middle Aged
  • Ovarian Neoplasms / etiology*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / metabolism
  • Programmed Cell Death 1 Receptor / metabolism*
  • Retrospective Studies
  • T-Lymphocytes / pathology*
  • T-Lymphocytes / physiology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor